The long-term objective of this program is to develop novel cancer immunotherapies based upon the ability of anti-T cell receptor (TCR) monoclonal antibodies (MoAbs) to stimulate immune responses. Specifically, the applicant plans to generate anti-clonotypic and anti-TCR MoAbs to T cell clones cytotoxic for melanoma. Anti-TCR antibodies suitable for future evaluation in cancer immunotherapy will be identified by their ability to enhance in vitro tumor cytotoxicity mediated by tumor-infiltrating lymphocytes (TIL) or peripheral blood lymphocytes (PBL) obtained from cancer patients. MoAbs which demonstrate the ability to induce tumor cytotoxicity will become candidates for future clinical trials to be performed during the phase II investigation. The applicant will also commence the characterization of the stimulatory anti-TCR MoAbs with respect to their specificity for TCR constant and variable region epitopes. This information should prove useful in generating additional MoAbs during the phase II period for future clinical evaluation in human subjects.